Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells
Tumor necrosis factor-alpha (TNF-α), a ubiquitous pro-inflammatory cytokine, is an important mediator in the immune-neuroendocrine system that affects the CNS. The present study demonstrates that treatment with TNF-α activates microglia to increase TNF-α production in primary cultures of glial cells...
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th-mahidol.198562018-07-12T09:49:27Z Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells J. Tangpong P. Sompol M. Vore W. St. Clair D. A. Butterfield D. K. St. Clair Walailak University University of Kentucky College of Medicine University of Kentucky Mahidol University Neuroscience Tumor necrosis factor-alpha (TNF-α), a ubiquitous pro-inflammatory cytokine, is an important mediator in the immune-neuroendocrine system that affects the CNS. The present study demonstrates that treatment with TNF-α activates microglia to increase TNF-α production in primary cultures of glial cells isolated from wild-type (WT) mice and mice deficient in the inducible form of nitric oxide synthase (iNOSKO). However, mitochondrial dysfunction in WT neurons occurs at lower concentrations of TNF-α when neurons are directly treated with TNF-α or co-cultured with TNF-α-treated microglia than iNOSKO neurons similarly treated. Immunofluorescent staining of primary neurons co-cultured with TNF-α-treated microglia reveals that the antioxidant enzyme in mitochondria, manganese superoxide dismutase (MnSOD), is co-localized with nitrotyrosine in WT but not in iNOSKO primary neuronal cells. Importantly, the percentage of surviving neurons is significantly reduced in WT neurons compared with iNOSKO neurons under identical treatment conditions. Together, the results suggest that TNF-α activates microglia to produce high levels of TNF-α and that production of nitric oxide (NO) in neurons is an important factor affecting MnSOD nitration and subsequent mitochondrial dysfunction. © 2008 IBRO. 2018-07-12T02:49:27Z 2018-07-12T02:49:27Z 2008-01-24 Article Neuroscience. Vol.151, No.2 (2008), 622-629 10.1016/j.neuroscience.2007.10.046 03064522 2-s2.0-37849010216 https://repository.li.mahidol.ac.th/handle/123456789/19856 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=37849010216&origin=inward |
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Neuroscience J. Tangpong P. Sompol M. Vore W. St. Clair D. A. Butterfield D. K. St. Clair Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells |
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Tumor necrosis factor-alpha (TNF-α), a ubiquitous pro-inflammatory cytokine, is an important mediator in the immune-neuroendocrine system that affects the CNS. The present study demonstrates that treatment with TNF-α activates microglia to increase TNF-α production in primary cultures of glial cells isolated from wild-type (WT) mice and mice deficient in the inducible form of nitric oxide synthase (iNOSKO). However, mitochondrial dysfunction in WT neurons occurs at lower concentrations of TNF-α when neurons are directly treated with TNF-α or co-cultured with TNF-α-treated microglia than iNOSKO neurons similarly treated. Immunofluorescent staining of primary neurons co-cultured with TNF-α-treated microglia reveals that the antioxidant enzyme in mitochondria, manganese superoxide dismutase (MnSOD), is co-localized with nitrotyrosine in WT but not in iNOSKO primary neuronal cells. Importantly, the percentage of surviving neurons is significantly reduced in WT neurons compared with iNOSKO neurons under identical treatment conditions. Together, the results suggest that TNF-α activates microglia to produce high levels of TNF-α and that production of nitric oxide (NO) in neurons is an important factor affecting MnSOD nitration and subsequent mitochondrial dysfunction. © 2008 IBRO. |
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Walailak University |
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Walailak University J. Tangpong P. Sompol M. Vore W. St. Clair D. A. Butterfield D. K. St. Clair |
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J. Tangpong P. Sompol M. Vore W. St. Clair D. A. Butterfield D. K. St. Clair |
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J. Tangpong |
title |
Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells |
title_short |
Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells |
title_full |
Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells |
title_fullStr |
Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells |
title_full_unstemmed |
Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells |
title_sort |
tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/19856 |
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1763497989941231616 |